Efficacy and Safety of the PET Imaging Agent [18F]NAV4694 in Subjects With Probable Alzheimer's Disease

NCT ID: NCT01680588

Last Updated: 2016-03-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2018-12-31

Brief Summary

This is a phase 2, open-label, multiple-center, non-randomized single dose study to assess the safety and efficacy of [18F]NAV4694 PET imaging in detecting beta-amyloid plaque in the brain in subjects with probable AD compared with healthy volunteers.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

[18F]NAV4694

Single intravenous injection of 8.1 millicuries of \[18F\]NAV4694

Group Type: EXPERIMENTAL

[18F]NAV4694

Intervention Type: DRUG

Interventions

[18F]NAV4694

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

All participants:

• is able to provide informed consent or assent, and exhibits adequate visual, auditory, and communication capabilities to enable compliance with study procedures
• should be able to perform the psychometric testing
• has a modified Hachinski score ((Hachinski, et al., 2012; Rosen, et al., 1980) ≤ 4 at screening
• possesses a general health that permits adequate compliance with all study procedures as ascertained by a detailed review of the medical history, surgical history, laboratory and physical examination findings, which must be performed within 56 days prior to administration of [18F]NAV4694
• informed consent has been signed and dated by the subject and/or the subject's legally authorized representative (LAR; for probable AD subjects)

Healthy Volunteers Only

• is male or female and is between the age of 18 and 40 years (for younger HVs) or 55 to 85 years of age (for older HVs)
• if female does not have childbearing potential: must be confirmed by either: post-menopausal status; or history of surgical sterilization or of hysterectomy
• if female has childbearing potential: must demonstrate a negative serum beta-HCG level at screening and a negative urine pregnancy test on the day of injection (prior to injection) consistent with a non-gravid state and agree to use two acceptable forms of birth control
• has no evidence of cognitive impairment as indicated by a clinical dementia rating (CDR) (Morris, 1993) score of 0 (zero) and a score of ≥ 28 in the Mini-Mental State Examination (MMSE) (Folstein, et al., 1975)
• has MRI brain scan that has been judged as "normal (age-appropriate)" supporting the lack of cerebrovascular disease (e.g., a white matter lesion score of 0, 1, or 2 and a basal ganglia score of 0 to 1 on the ARWMC scale)

Probable Alzheimer's Disease Subjects Only

• is male or female and is ≥ 55 of age, whereby females must be without childbearing potential (confirmed by either:post-menopausal status; or history of surgical sterilization or of hysterectomy)

Exclusion Criteria

• does not fulfill the International Consensus Criteria (ICC) for probable diffuse Lewy body disease (DLBD), the NINDS-AIREN for probable vascular dementia, or the Neary criteria for frontotemporal dementia (FTD) [Neary et al. 1998]
• has a MMSE score between 16 and 23
• has a CDR (Morris, 1993) score of 1 to 2
• has a Cornell Scale for Depression in Dementia (CSDD; (Alexopoulos, et al., 1988)) score less than or equal to 18 (definite major depression)
• MRI brain scan findings that do not reveal changes indicative of stroke and/or generalized cerebrovascular disease changes (limited to: a white matter lesion score of 0, 1, or 2 and a basal ganglia score of 0 or 1 on the ARWMC scale)
• has a caregiver who is willing and able to attend study visits and perform the psychometric tests requiring the presence of a caregiver

• has any contraindication to MRI examination, e.g., metal implants or phobia
• is not able to lie down flat in the MRI and PET scanners
• is scheduled for surgery and/or another invasive procedure within the time period of up to 10 days after [18F]NAV4694 application
• is medically unstable and whose clinical course during the observation period is unpredictable, e.g., subjects within 14 days of myocardial infarction or stroke, unstable subjects with previous surgery (within 7 days), subjects with advanced heart insufficiency (NYHA stage IV), or with acute renal failure
• has a history of exposure to any radiation > 30 mSv in the last year (e.g., occupational, diagnostic imaging, or radiation therapy)
• is receiving drug therapy or other treatment that is known to lead to greatly fluctuating values of the hematological or chemical laboratory parameters or to severe side effects (e.g., chemotherapy)
• has received anti-amyloid immunotherapy
• has been previously enrolled in this study and received [18F]NAV4694 or participated in a clinical study involving an investigational pharmaceutical product within 30 days prior to screening, and/or any radiopharmaceutical within 10 radioactive half-lives prior to [18F]NAV4694 administration
• has a brain tumor or other intracranial lesion, a disturbance of cerebrospinal fluid (CSF) circulation (e.g., normal pressure hydrocephalus) and/or a history of serious head trauma or brain surgery
• has a history, physical, laboratory, or imaging findings indicative of a significant neurological or psychiatric illness (other than AD for the subjects with probable AD)
• has another untreated disease that can cause disturbance of brain function (e.g. vitamin B12 or folic acid deficiency, disturbed thyroid function, anemia)
• has a history of alcohol abuse or drug dependency in the 3 years prior to study entry or is an alcoholic or drug addict as determined by the investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Navidea Biopharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cornelia Reininger, M.D., PhD

Role: STUDY_DIRECTOR

Navidea Biopharmaceuticals

Locations

Molecular NeuroImaging, LLC

New Haven, Connecticut, United States

Rush University Medical Center

Chicago, Illinois, United States

Alexian Brothers Neurosciences Institute

Elk Grove Village, Illinois, United States

Indiana Medical Research

Indianapolis, Indiana, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

Alzheimer's Disease Center, Quincy Medical Center

Quincy, Massachusetts, United States

Neurological Associates of Albany

Albany, New York, United States

Countries

United States

Other Identifiers

NAV4-01

Identifier Type: -

Identifier Source: org_study_id